Biologically oriented organic sulfur chemistry. 7. Carbonyl disulfides as inhibitory agents for Histoplasma capsulatum

Abstract

lithium in dry Et20 under Nj at -70°. After 2 hr the mixture was warmed to room temp and hydrolyzed (H20). The resulting a-(2-pyridyl) 6-methyl-2-trifluoromethyl-4-quinolyl ketone was reerystd from EtOH (30%) mp 155°( lit.8 mp 153°). The results of these experiments are shown in Table II.As might have been expected the reaction between 4-quinolyllithiums and pipecolenic acid which has two active hydrogens and would form a dianion with two proximate negative charges, Field, et al.failed to give the piperidyl ketone; in the case of the 6-Me derivative the corresponding parent quinoline was obtained in 55% yield.The reaction of 4-cyano-6,8-dimethyl-2-trifluoromethylquinoline (13s) with 2-PyLi in Et20 at -70°for 4 hr under N2 and purification by column chromatography on silica gel (CHC13) gave 50%c of 2-pyridyl 6,8-dimethyl-2-trifluoromethyl-4-quinolyl ketone, mp 94°( lit.8 mp 98°).

Reactions of ketene thioacetals with electrophiles. Homologation of aldehydes

“…Seven possible approaches were compared in preparing the acetyl disulfides [1][2][3][4][5][6][7][8][9][10][11] shown in Table I. The sulfenyl chloride method of eq 1, employed in the preparation of unfunctionalized carbonyl disulfides,3 was 0.501, 0.5C12 AcSH RSH->0.5(RS)2->RSC1-> AcSSR + HC1 (1) unpromising except for the preparation of 1 and 11.…”

Organic disulfides and related substances. 32. Preparation and decomposition of .beta.-substituted ethyl acetyl disulfides

“…Procedure C. .-Essentially the method of Bohme and Clement was used to prepare [1][2][3][4][5][6][7]8 except that the sulfenyl chloride 16 was prepared in CH2C12 and used without isolation. Acetylsulfenyl chloride (16) was prepared under a N2 atmosphere at -15°from Ac2S (37 g, 0.31 mol) in 50 ml of CH2C12 and Cl2 (21 g, 0.29 mol) in 75 ml of CH2C12.…”

“…The preparation and investigation of //-substituted ethyl acetyl disulfides, i.e., of AcSS(CH2)2X, had a twofold purpose: (a) to clarify the importance of functional group assistance to acetyl-sulfur and/or sulfursulfur cleavage with //-substituted disulfides and to compare the relative effectiveness of functional groups; and (b) to determine whether these functional groups would lead to a greater inhibitory effect than was found for methyl acetyl disulfide on H. capsulatum, a fungal pathogen for man. 3 Seven possible approaches were compared in preparing the acetyl disulfides [1][2][3][4][5][6][7][8][9][10][11] shown in Table I. The sulfenyl chloride method of eq 1, employed in the preparation of unfunctionalized carbonyl disulfides,3 was 0.501, 0.5C12 AcSH RSH->0.5(RS)2->RSC1-> AcSSR + HC1 (1) unpromising except for the preparation of 1 and 11.…”

“…The procedure of Mukaiyama and Takahashi was unsatisfactory in our hands for the preparation of liquid acetyl disulfides (eq 3).6 An attempt to prepare phenyl AcSH + Et02CN=NC02Et -> RSH Et02CN(SAc)NHC02Et -> AcSSR (3) 13 acetyl disulfide by this procedure was unsuccessful, as was an attempt to purify the intermediate 13; the nmr spectrum of the distilled 13 had appropriate peaks, but the ratios of protons were inconsistent with pure 13. When the addition was reversed, benzenethiol being added first•, 44% of phenyl acetyl disulfide was isolated (the ir spectrum was identical with that of an authen-tic2® sample).…”

“…Purification of [1][2][3][4][5][6][7][8][9][10][11] presented no great problems. Solids could be recrystallized (2, 5, 7, 9, 10), and two liquids (6, 11) could be distilled using a highly efficient column.…”